Biological characterisation of [67Ga] or [68Ga] labelled DFO-octreotide (SDZ 216-927) for PET studies of somatostatin receptor positive tumors.

Abstract

Radiolabelled analogues of Somatostatin (SRIF) were demonstrated to be useful for conventional gamma-camera imaging of SRIF receptor-positive tumors and their metastases. To evaluate the feasibility of positron emission tomography (PET) or SRIF receptor-positive tumors deferoxamine (DFO) was conjugated to octreotide via a succinyl linker to form a stable conjugate with the gallium isotopes 67Ga and 68Ga. This new octreotide analog, SDZ 216-927, binds specifically and with high affinity to SRIF receptors in vitro (pKi = 8.94 +/- 0.06) and exhibits SRIF like biological properties as demonstrated by the inhibition of growth hormone (GH) release from cultured pituitary cells. SDZ 216-927 was efficiently labelled with 67Ga without affecting high affinity binding to SRIF receptors. Biodistribution studies revealed that [67Ga]SDZ 216-927 was stable in vivo and rapidly cleared from the circulation, as indicated by the low amount of 67Ga detected in the blood four hours post injection (p.i.). SRIF receptor-positive tumors were clearly visualized 10 minutes p.i. in tumor bearing rats. The specificity of ligand binding in vivo was demonstrated i) by the high tumor/non-tumor ratio 4 hours p.i. (tumor/blood 22.3:1, tumor/muscle 64.5:1, tumor/liver 4.0:1, tumor/spleen 16.8:1) and ii) by a significantly lower uptake of radioactivity in the tumor after pretreatment of tumor bearing animals with an excess of unlabelled SDZ 216-927. SDZ 216-927, when labelled with the positron emitting isotope 68Ga, clearly imaged SRIF receptor-positive tumors using positron emission tomography (PET). Therefore quantitative SRIF receptor imaging with PET seems to be possible using this new radiopharmaceutical.

• Authors: B Stolz, P M Smith-Jones, R Albert, H Reist, H Mäcke, C Bruns
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 26 Issue 10 Pg. 453-9 (Oct 1994) ISSN: 0018-5043 [Print] Germany
• PMID: 7851867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Gallium Radioisotopes
• Receptors, Somatostatin
• desferrioxamine B-succinyl-phenylalanine(1)-octreotide
• Deferoxamine
• Octreotide

Topics

• Animals
• Carrier Proteins (metabolism)
• Deferoxamine (analogs & derivatives, metabolism, pharmacokinetics)
• Gallium Radioisotopes
• In Vitro Techniques
• Octreotide (analogs & derivatives, metabolism, pharmacokinetics)
• Pancreatic Neoplasms (chemistry, diagnostic imaging)
• Rats
• Receptors, Somatostatin (analysis)
• Tomography, Emission-Computed